This invention relates to certain novel analogs of the naturally occurring prostaglandins. In particular, it relates to novel 2-descarboxy-2-[tetrazol-5-yl]-.omega.-pentanorprostaglandins and various novel intermediates useful in their preparation.
The prostaglandins are C-20 unsaturated fatty acids which exhibit diverse physiological effects. For instance, the prostaglandins of the E and A series are potent vasodilators (Bergstrom, et al., Acta Physiol. Scand. 64:332-339, 1965 and Bergstrom, et al., Life Sci. 6:449-455, 1967). This relaxant effect on small blood vessels probably accounts for the fall in systemic arterial blood pressure (vasodepression) observed on intravenous injection of PGE.sub.1 and PGA.sub.1 (Weeks and King, Federation Proc. 23:327, 1964; Bergstrom, et al., 1965, op. cit.; Carlson, et al., Acta Med. Scand. 183:423-430, 1968; and Carlson, et al., Acta Physiol. Scand. 75:161-169, 1969). Another well known physiological action for PGE.sub.1 and PGE.sub.2 is as a bronchodilator (Cuthbert, Brit. Med. J. 4:723-726, 1969).
Another important physiological role for the natural prostaglandins is in connection with the reproductive cycle. PGE.sub.2 is known to possess the ability to induce labor (Karim, et al., J. Obstet Gynaec. Brit. Cwlth. 77:200-210, 1970) and also to induce therapeutic abortion (Bygdemon, et al., Contraception, 4, 293 (1971) and to be useful for control of fertility (Karim, Contraception, 3, 1973 (1971). Patents have been obtained for several prostaglandins of the E and F series as inducers of labor in mammals (Belgian Pat. No. 754,158 and West German Pat. No. 2,034,641), and on PGF.sub.1, F.sub.2, and F.sub.3 for control of the reproductive cycle (South African Pat. No. 69/6089.
Still other known physiological activities for PGE.sub.1 are in the inhibition of gastric acid secretion (Shaw and Ramwell, In: Worcester Symp. on Prostaglandins, New York, Wiley, 1968, p. 55-64) and also of platelet aggregation (Emmons, et al. Brit. Med. J. 2:468-472, 1967).
It is now known that such physiological effects will be produced in vivo for only a short period, following the administration of a prostagladin. A substantial body of evidence indicates that the reason for this rapid cessation of activity is that the natural prostaglandins are quickly and efficiently metabolically deactivated by .beta.-oxidation of the carboxylic acid side-chain and by oxidation of the 15.alpha.-hydroxyl group (Anggard, et al., Acta. Physiol. Scand., 81, 396 (1971) and references cited therein).
It was, of course, considered desirable to create analogs of the prostaglandins which would have physiological activities equivalent to the natural compounds, but in which the selectivity of action and the duration of the activity would be increased.